This invention relates to a tetrahydrofuran antifungal phosphate which is named: 5-[[2(S)-[4-[4-[4-[4-[[(R-cis)-5-(2,4-difluorophenyl)-tetrahydro-5-(1H-1,2 ,4-triazol-1-ylmethyl)-3-furanyl] methoxy]phenyl]-1-piperazinyl]phenyl]-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1 -yl]-1(S)-methylbutyl]oxy]-5-oxobutyl phosphate, and to a tetrahydrofuran antifungal butyrate which is named: (-)-2(S)-[4-[4-[4-[4-[[(R-cis)-2-(2,4-difluorophenl) tetrahydro-2- (1H-1,2,4-triazol-1-ylmethyl)-4-furanyl]methoxy]phenyl]-1-piperazinyl]phen yl]-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl]-1(S)-methylbutyl 4-hydroxybutanoate and pharmaceutically acceptable salts thereof, pharmaceutical compositions containing such antifungals and methods of treating or preventing fungal infections in hosts using them.
International Publication Nos. WO 96/38443 (published Dec 5, 1996) and WO 95/17407 (published Jun. 29, 1995) disclose various tetrahydrofuran antifungals and phosphate esters thereof but neither one discloses the tetrahydrofuran antifungal compounds of the present invention.
There is a need for a broad spectrum antifungal agent having solubility suitable for parenteral administration and a favorable activity profile for treating and/or preventing systemic fungal infections, especially Aspergillus, Candida, Cyrptococcus and opportunistic infections.